Thymoquinone, 2-isopropyl-5-methyl-1,1,4-benzoqinone (TQ), can be extracted from black seed (Nigella sativa) oil and has been reported as an anticancer agent in cancer cells. The anticancer effects of TQ on malignant tumours with selectivity towards cancer cells over normal cell has been discussed in Aggarwall B B et al (2008) Planta Med vol. 74(13) pp 1560-1569. Thymoquinone analogs have also been proposed for the use in treating pancreatic cancers, for example in WO2011126544.
The end caps of human chromosomes, telomeres, are known to protect DNA chromosomes against degradation, non-homologous end-stacking and nuclease attacks. Telomeres are shortened after each cell division till the cell loses its functions and apotosis. The telomerase enzyme, found active in most cancer cells, re-elongates the telomere and maintains its length causing cancer cell to continue to divide indefinitely. Telomeres comprise tandem repeats enriched in guanine bases that fold up in physiological conditions to form four-stranded DNA called G-quadruplex. Folding single stranded telomeric DNA into G-quadruplex structure has been shown to inhibit the telomerase enzyme, overexpressed in cancer cells.
Small molecules that bind and stabilise G-quadruplex DNA have been found to inhibit the telomerase enzyme in cancer cells and subsequently inhibit DNA replication and cancer cell proliferation, Huppert J L (2007), Phil. Trans. A. Math. Phys. Eng. Sci., vol. 365(1861) pp 2969-2984. Therefore molecules with high preferential affinity towards G-quadruplex DNA have been seen as a potential avenue of compounds for developing new anticancer therapeutic agents.
Accordingly it is an object of the invention to provide further thymoquinone derivatives that may be effective in cancer treatment.